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  • Title: In vivo real-time fluorescence visualization and brain-targeting mechanisms of lipid nanocarriers with different fatty ester:oil ratios.
    Author: Wen CJ, Yen TC, Al-Suwayeh SA, Chang HW, Fang JY.
    Journal: Nanomedicine (Lond); 2011 Nov; 6(9):1545-59. PubMed ID: 22077462.
    Abstract:
    AIMS: The objective of the present work was to investigate the influence of the inner cores of lipid nanocarriers on the efficiency of brain targeting. Cetyl palmitate and squalene were respectively chosen as the solid lipid and liquid oil in the inner phase of the nanocarriers. MATERIALS & METHODS: Nanoparticulate systems with different cetyl palmitate/squalene ratios were compared by evaluating the size, zeta potential, molecular environment, and mobility of lipids in the systems. RESULTS: The particulate diameter ranged from 190 to 210 nm, with systems containing 100% cetyl palmitate in the matrix (solid lipid nanoparticles [SLN]) showing the smallest size, followed by systems with both cetyl palmitate and squalene (nanostructured lipid carriers [NLC]) and with 100% squalene (lipid emulsions [LE]). A cationic surfactant, Forestall, was used to produce a positive surface charge of 40-55 mW. The in vitro release was evaluated using various dyes located in different phases of the nanocarriers. The release of sulforhodamine B occurred in a sustained manner from the shell of the nanocarriers. The in vivo brain distribution of lipid nanosystems after an intravenous injection into rats was monitored by a real-time fluorescence imaging system. LE showed higher brain accumulation than SLN and NLC. NLC only exhibited a slightly higher brain accumulation compared with the aqueous control. Incorporation of sulforhodamine B into LE could prolong its retention in the brain from 20 to 50 min. The results were further confirmed by imaging the entire brain and brain slices. The specific association of lipid nanocarriers with rat brain endothelial cells (bEnd3) was demonstrated using fluorescence microscopy. The cellular uptake of LE and SLN was higher compared with NLC and the aqueous control. LE were observed to be internalized by cells through caveola-mediated and macropinocytotic energy-dependent endocytosis. CONCLUSION: The experimental profiles indicated that LE with moderate additives are a promising brain-targeting nanocarrier. The composition of the lipid matrix played a significant role in delivering compounds to the brain.
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